Bacteremic infection caused by polysaccharide encapsulated organisms is a major cause of morbidity and mortality in infants and children. Observations made over decades ago demonstrated that young children, particularly those less than 2 years, are at increased risk for suffering episodes of bacteremia caused by encapsulated bacteria and that these episodes can lead to serious even fatal illness. Recent observations in children with HIV infection have also underscored the importance of these pathogens in these immunocompromised patients. Although antibacterial agents are highly effective in treating these infections, it remains difficult to accurately diagnose these patients at the time of presentation. Without improved diagnostic tools or prevention strategies that significantly reduce the incidence of these infections, thousands of children will continue to be given antimicrobials or even to be hospitalized unnecessarily. An incomplete understanding of the immunology of these infections has been a major obstacle to advances in this field. Recent work has demonstrated that complex cellular responses within the reticuloendothelial system are associated with bacteremic infection and that certain proteins (cytokines) that mediate cell movement, proliferation and activation determine this response. This new information serves as the basis for examining the association of serum cytokine levels with severe infection in infants. In the proposed work, measurement of factors known to either directly or indirectly mediate cellular responses characteristic of bacteremic infection caused by encapsulated bacteria will be measured in children and infants with febrile illnesses. Levels will be assessed during the course of bacteremic and nonbacteremic illnesses in infants and children and association between these levels and severity and type of infection, age of patient and outcome will be determined. Infants and children with HIV infection will be included in this study and data collected in these patients will be compared to otherwise healthy patients to determine if deficient responses explain the association of HIV infection and unique susceptibility to severe bacteremic infection. It is expected that this work will improve our understanding of the immunology of these infections. A more complete understanding of host defenses to these infections will improve our ability to recognize and treat these infections.